Implication of decreased expression of Fatty-Acid Desaturases in Accutane-induced bowel diseases

accutane
roaccutane
isotretinoin
#1

A study of changes in gene expression in skin after 8 weeks of isotretinoin treatment found a several-fold decrease in the levels of mRNA encoding two isoforms of fatty-acid desaturases. FADS1 decreased 4.9 fold and FADS2 by 3.37-fold :

A. M. Nelson, W. Zhao, K. L. Gilliland, A. L. Zaenglein, W. Liu, and D. M. Thiboutot, “Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action,” Dermato-Endocrinology , vol. 1, no. 3, pp. 177–187, May 2009.

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Associations between polymorphisms of the FADS genes and disease have been made:

Ž. A et al. , “[Desaturases of fatty acids (FADS) and their physiological and clinical implication].,” Cas Lek Cesk , vol. 155, no. 2, pp. 15–21, 2016.

Associations of some SNP FADS with coronary heart disease, concentrations of plasma lipids, oxidative stress, glucose homeostasis, and inflammatory reaction, were described.

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A. Franke et al. , “Meta-Analysis Increases to 71 the Tally of Confirmed Crohn’s Disease Susceptibility Loci,” Nature genetics , vol. 42, no. 12, p. 1118, Dec. 2010.

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In addition, genetic kncok-out of the FADS2 gene in mice let to a phenotype with a drastically increased susceptibility to development of intestinal ulceration.

C. K. Stroud et al. , “Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration**,” J. Lipid Res. , vol. 50, no. 9, pp. 1870–1880, Sep. 2009.

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IMO this is something that was neglected to be addressed in all previous investigation of the link between Accutane and IBS, IBD, and Crohn’s and shows a strong association between the two.